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High hydrostatic pressure has been shown to reverse the anesthetic effects of barbiturates. However, attempts to distinguish between two possible causes of this reversal, changes in drug disposition or changes in drug-receptor interaction, have not been reported. This study examined the possible effects of hyperbaria and hyperbaric hyperoxia on the distribution and clearance of pentobarbital in the dog. The drug was administered to six mixed-breed dogs as a 30 mg/kg i.v. bolus at 1 ATA breathing air, 6 ATA breathing air, and 2.8 ATA breathing 100% oxygen, with serial blood sampling for 12 h. Pharmacokinetic and statistical analyses showed no significant effects of hyperbaria or hyperbaric hyperoxia on the total plasma clearance, volume of distribution or elimination half-life. If pressure reversal of barbiturate anesthesia occurs at these pressures, changes in the disposition of the drug are not the causative factors.

Thirty adult, male, Long-Evans hooded rats underwent spinal cord transections at the T5 vertebral level. Following surgery, animals were separated into three groups: Group I received only normal postoperative care; Group II received daily hyperbaric oxygen (HBO) treatments for 47-54 consecutive days; Group III received the same HBO treatment as Group II in addition to subcutaneous injections of dimethyl sulfoxide (DMSO) for 10 consecutive days. All animals were killed 60-70 days postlesion. The lesioned area of spinal cord was removed and prepared for light and electron microscopy. Group I animals showed typical scar reduction of cavitations, increased scarring, and more nerve fibers within the lesion. Three animals in this group exhibited coordinated hindlimb movement, with one animal showing weight-bearing ability. The lesion sit in group III animals revealed a reduction in collagen formation and a further increase in the number of nerve fibers. Six animals in Group III showed coordinated hindlimb movements; among these two displayed weight-bearing ability and sensory return.

Five different experiments were conducted to determine if estimated liver plasma flow and/or plasma volume were changed as a result of exposure to 2.8 atmospheres absolute (ATA) while breathing 100% oxygen or 6 ATA while breathing compressed air. The experiments were designed to separate the relative roles of the ambient pressure, the partial pressure of oxygen, the time of high oxygen exposure or some combination of these factors on any observed changes. We found that time was not a factor in the changes seen. Hyperbaria resulted in a decrease in estimated liver plasma flow at all pressures greater than 1 ATA. There was an apparent increase in plasma volume at 1.3 ATA and a return towards 1 ATA values at higher pressures. Hyperoxia resulted in a decrease in estimated liver plasma flow at 975 mm Hg but not at 912 mm Hg. The flow was then increased again at 2128 mm Hg. Plasma volume decreased significantly at 912 mm Hg returned to baseline (152 mm Hg) values at 975 mm Hg and then decreased again at 1054 and 2128 mm Hg PO2.

Six groups of six conditioned dogs each were instrumented with an electromagnetic flow-meter transducer around the pulmonary artery, and indwelling silastic cannulae in the pulmonary artery, the left ventricle, the ascending aorta, and the right atrium. After allowing a minimum of 5 d for recovery, the dogs were studied under normobaric conditions, breathing air, at 2.8 atmospheres absolute (ATA), breathing 100% oxygen (PO2 2128 mm Hg) and at 6 ATA breathing air (PO2 960 mm Hg). Baseline recordings were made at 1 ATA and repeated after arrival at depth. The dogs were hemorrhaged until the mean aortic pressure fell to 40 mm Hg. Mean aortic pressure was maintained between 40-50 mm Hg for 30 min. This required a rather constant 40 +/- 4.5 ml X kg-1 body weight of total blood removed. Three groups, one at each depth perturbation, were then given Dextran 70, the other three groups 10% dextrose. Fluids were administered at a constant rate until the mean aortic pressure rose to within 90% of its original 1 ATA baseline value. At this point, the infusion was stopped and the total amount of fluid administered was recorded. Hemodynamic parameters were measured or calculated for eight different time periods during each experiment. The amount of Dextran 70 required did not change with hyperbaric exposure but only half as much 10% dextrose was required at depth. Dextran 70 held the cardiovascular parameters constant for 30 min following administration but after 10% dextrose, cardiac output tended to decrease at 15 and 30 min posttreatment. There were no significant differences in the cardiovascular effects of hemorrhage between or among the dogs exposed to the three different environmental conditions.

Hyperbaric air and hyperbaric hyperoxia, which have been shown to decrease both liver plasma flow and plasma volume in dogs, may potentially affect the disposition of drugs whose distribution and/or elimination are dependent upon those actions. This study examined the effects of those conditions on the disposition of salicylic acid, using the dog as a model. The drug was administered to six mixed-breed dogs as a 10 mg sodium salicylate/kg i.v. bolus at 1 ATA breathing air (control), at 2.8 ATA breathing 100% O2, and at 6 ATA breathing air, followed by serial blood sampling for 8 h. Statistical analysis showed a significant increase (p less than 0.05) in salicylate clearance at 2.8 ATA compared to control with a subsequent, although not statistically significant, increase in elimination half-life. There were no significant differences between the values observed at 6 ATA and either control or 2.8 ATA. As 100% O2 at 2.8 ATA is used during hyperbaric oxygen medical therapy and during decompression, this change in disposition of this commonly used agent may have implications in man. Studies in man must be conducted, however, to determine if the same conclusions apply.

There are several reports of secretory and other abnormalities present in cultured fibroblasts from patients with cystic fibrosis (CF). We have, therefore, investigated aspects of complex saccharide synthesis and secretion by such cells compared with fibroblasts derived from heterozygous (HZ) parents and from normal (N) children. The main glycosaminoglycans produced by skin fibroblasts during in vitro culture were hyaluronic acid, heparan sulfates, and dermatan sulfate-like materials. Using double-label experiments with D-[3H]- or [14c]glucosamine and analyzing the products by ion exchange chromatography, it was shown for five CF, two HZ, and four N lines that these polysaccharides were secreted into the medium in approximately similar proportions to each other. Moreover, experiments in which three CF, nine HZ, and three N lines were grown in log phase for up to 5 days in the presence of [35S]sulfate and [3H]glucosamine indicate that, during such a period, CF fibroblasts do not secrete complex carbohydrates at rates significantly different from N or HZ cells. Neither do such cells shown an abnormal intracellular accumulation of complex carbohydrates. The latter observation was further confirmed by preparing whole cell autoradiographs during growth of six CF, two HZ, and three N lines in the presence of D-[3H]glucosamine and, subsequently, after addition of unlabeled medium.

Three groups of six dogs each were instrumented with an electromagnetic flow-meter around the pulmonary artery, and indwelling silastic cannulas in the pulmonary artery, the left ventricle, the ascending aorta and the right atrium. After allowing 5-7 d for recovery the dogs were studied under normobaric conditions, breathing air, at 2.8 atmospheres absolute (ATA) breathing 100% oxygen (PO2 approximately equal to 2128 mm Hg) and at 6 ATA breathing air (PO2 approximately equal to 960 mm Hg). Baseline recordings were made at 1 ATA and repeated after arrival at depth. The dogs were hemorrhaged until the mean aortic pressure fell to 40 mm Hg. Mean aortic pressure was maintained between 40-50 mm Hg for 30 min. Enough lactated Ringer's solution was then infused to stabilize the aortic pressure to within 90% of its original 1 ATA baseline value. Hemodynamic parameters were measured or calculated at eight different times. There were statistically significant differences in some of the measured parameters due to the effects of hemorrhage but no differences between the three groups attributable to either of the hyperbaric conditions or the effects of lactated Ringer's solution.

Two methods for estimating body surface area (BSA) in adult amputees were developed. BSA in sq m was determined in 42 healthy, nonamputee men and women by summing the surface areas of individual body parts obtained using geometric measurements (BSAmeas) and by an equation using height and weight (BSAcalc). Linear regression analysis was used to determine correlations between BSAmeas and BSAcalc and between BSAmeas and surface-area measurements of individual body parts (SApart). The percentages of total BSA contributed by individual body parts in each subject were determined by the ratio of SApart to BSAmeas, and these percentages were compared with the corresponding percentages for body parts using the "Rule of Nines." BSAcalc and BSAmeas were significantly correlated, as were SApart and BSAmeas. Regression analysis of SApart versus BSAmeas yielded an equation for each measured body part that allowed calculation of SApart without direct measurement. SApart expressed as a percentage of total BSA differed from the percentage of BSA used in the "Rule of Nines" by a mean of 12.4-32% depending on the body part. Two methods of estimating BSA in amputees were proposed based on deduction of the surface area of the amputated part (calculated from the regression equation for SApart or as a percentage of total BSA) from total BSAcalc in adult amputees. The two methods developed in this study for estimating BSA may be useful in determining drug dosages in adult amputees and may provide more accurate information in burn therapy. Further studies are needed to validate the clinical application of these methods.